11-113415779-A-G

Variant names:

• chr11-113415779-A-G
• rs2734838
• NM_000795.4:c.533-168T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000795.4(DRD2):​c.533-168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,084 control chromosomes in the GnomAD database, including 17,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (17348 hom., cov: 32)
• Consequence: DRD2 NM_000795.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.202
• Publications: 23 publications found

Genes affected

DRD2 (HGNC:3023): (dopamine receptor D2) This gene encodes the D2 subtype of the dopamine receptor. This G-protein coupled receptor inhibits adenylyl cyclase activity. A missense mutation in this gene causes myoclonus dystonia; other mutations have been associated with schizophrenia. Alternative splicing of this gene results in two transcript variants encoding different isoforms. A third variant has been described, but it has not been determined whether this form is normal or due to aberrant splicing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-113415779-A-G is Benign according to our data. Variant chr11-113415779-A-G is described in ClinVar as Benign. ClinVar VariationId is 1250420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000795.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	NM_000795.4	MANE Select	c.533-168T>C		intron	N/A	NP_000786.1
	DRD2	NM_001440368.1		c.530-168T>C		intron	N/A	NP_001427297.1
	DRD2	NM_016574.4		c.533-168T>C		intron	N/A	NP_057658.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD2	ENST00000362072.8	TSL:1 MANE Select	c.533-168T>C		intron	N/A	ENSP00000354859.3
	DRD2	ENST00000542968.5	TSL:1	c.533-168T>C		intron	N/A	ENSP00000442172.1
	DRD2	ENST00000544518.5	TSL:1	c.530-168T>C		intron	N/A	ENSP00000441068.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66793 AN: 151966 Hom.: 17359 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.0588

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.501

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.439 AC: 66787 AN: 152084 Hom.: 17348 Cov.: 32 AF XY: 0.429 AC XY: 31888 AN XY: 74324

African (AFR) AF: 0.211 AC: 8761 AN: 41510

American (AMR) AF: 0.392 AC: 5989 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2229 AN: 3466

East Asian (EAS) AF: 0.0583 AC: 302 AN: 5178

South Asian (SAS) AF: 0.364 AC: 1751 AN: 4814

European-Finnish (FIN) AF: 0.476 AC: 5029 AN: 10574

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40866 AN: 67952

Other (OTH) AF: 0.497 AC: 1046 AN: 2104

Alfa AF: 0.560 Hom.: 71684

Bravo AF: 0.426

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.020
DANN	Benign	0.22
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2734838; hg19: chr11-113286501;